Nanobody-Based CD19/CD20 Tandem Dual CAR-T-cell Therapy of Relapsed/Refractory B-Cell Lymphoma

Официальное название

Clinical Study on the Safety and Efficacy of Nanobody-Based CD19/CD20 Tandem Dual CAR-T-cell Therapy for Relapsed/Refractory B-Cell Lymphoma

Обзор

This is a single arm study to evaluate the safety and efficacy of Nanobody-Based CD19/CD20 Tandem Dual CAR-T-cell therapy for Relapsed/Refractory B-Cell Lymphoma

Вмешательства

• Генная терапия CD19/CD20 Tandem Dual CAR-T
  Each subject will be infused with single dose of CD19/CD20 Tandem Dual CAR-T. A classic "3+3" dose escalation will be employed. The low dose is 2×10\^6 / kg, the medium dose is 4×10\^6 /kg, and the high dose is 6×10\^6 /kg.

Первичные конечные точки

• According to the incidence of treatment-related adverse events (AEs) to evaluate the safety of Nanobody-Based CD19/CD20 Tandem Dual CAR-T-cell therapy for CD20/CD19 positive relapsed/refractory B-Cell lymphoma. [Срок оценки: up to 3 years]
• According to the determine the Maximal Tolerable Dose(MTD) to evaluate the safety of Nanobody-Based CD19/CD20 Tandem Dual CAR-T-cell therapy for CD20/CD19 positive relapsed/refractory B-Cell lymphoma. [Срок оценки: MTD will be determined based on DLTs observed during the first 28 days of study treatment]

Вторичные конечные точки (1)

• According to the objective response rate (ORR) to evaluate the efficacy of Nanobody-Based CD19/CD20 Tandem Dual CAR-T-cell therapy for CD20/CD19 positive relapsed/refractory B-Cell lymphoma. [Срок оценки: Within 3 months following infusion of CD19/CD20 Tandem Dual CAR-T]

Критерии участия

Критерии включения

• The subject has voluntarily signed the informed consent form with full consent, and is willing and able to comply with the scheduled visits, study treatments, laboratory tests, and other trial procedures
• Patients with relapsed/refractory B-cell lymphoma confirmed by cytology or histology according to the WHO 2022 Classification:

• Lymphoma cells confirmed to express CD19 and/or CD20 antigen by immunophenotyping or histopathological immunohistochemistry
• B-cell lymphomas include: aggressive B-cell lymphomas (LBCL, BL, MCL) and indolent B-cell lymphomas (CLL/SLL, FL, MZL, LPL, HCL)
• Relapsed/refractory B-cell lymphoma: For patients with aggressive lymphoma, disease stable for ≤12 months or disease progression after achieving best response following at least first- and second-line pharmacotherapy; or disease progression or relapse within ≤12 months after autologous stem cell transplantation. For patients with indolent lymphoma, disease progression, relapse or transformation following at least three lines of prior therapy
• Aged 18-75 years (inclusive), male or female
• Subjects with an Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2
• Estimated overall survival of more than 3 months from the date of signing the informed consent form
• Hemoglobin (HGB) ≥ 70 g/L (transfusion permitted)
• Adequate hepatic, renal and cardiopulmonary function meeting the following criteria:

• Creatinine ≤ 1.5 × ULN;
• Left ventricular ejection fraction (LVEF) ≥ 50%;
• Blood oxygen saturation > 90%;
• Total bilirubin ≤ 1.5 × ULN; ALT and AST ≤ 2.5 × ULN
• The subject agrees to use contraceptive measures from the date of signing the informed consent form until 1 year after CAR-T cell infusion

Критерии исключения

• Severe cardiac insufficiency with left ventricular ejection fraction < 50%
• History of severe pulmonary function-impairing diseases
• Concomitant other advanced malignant neoplasms
• Concomitant severe infection that cannot be effectively controlled
• Concomitant severe autoimmune diseases or congenital immunodeficiency disorders
• Active hepatitis (hepatitis B virus deoxyribonucleic acid \[HBV-DNA\] or hepatitis C virus ribonucleic acid \[HCV-RNA\] test result above the lower limit of detection)
• Human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome (AIDS), or syphilis infection
• History of severe allergy to biological products (including antibiotics)
• Patients with allogeneic hematopoietic stem cell transplantation who still have acute graft-versus-host disease (GVHD) after one month of discontinuation of immunosuppressive agents

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT07546630 · VHH CAR2019-XYBYXB

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗